Propagation of action potentials AP in axons relies on the concerted action of membrane-spanning selectively permeable ion channels Hodgkin and Huxley, This mode of conduction allows faster Rushton, ; Waxman and Bennett, and more reliable Kuriscak et al.
In contrast, only unmyelinated axons, which are generally feature uniformly distributed ion channels Black et al. The number of ion channels on the surface of neurons' membrane is usually thought to be large enough to justify combining the individual channel conductances into a continuous measure of overall conductivity Dayan and Abbott, , as originally done by Hodgkin and Huxley However in the case of thin axons, the number of ion channels may be too small for these approximations to be valid.
Faisal and Laughlin showed that in order to accurately model thin axons, the behavior of individual ion channels needs to be taken into account. Channel noise in very thin axons has a large effect, limiting the miniaturization of fibers by imposing a lower diameter on axons at 0.
The conceptual transition from conductivity per surface area to density of channels, with each channel having only two possible conductance value corresponding to its open and closed states, involves investigating the effects of possible non-uniformities in the distribution of ion channels across the membrane. Based on observations from the neonatal rat optic nerve, Waxman et al.
Faisal and Laughlin showed that probabilistic gating of ion channels due to thermodynamic fluctuations, or channel noise reviewed by White et al. They are typically 0. Disassociating lipid rafts and Nav1. C-fibers are very thin unmyelinated peripheral axons responsible for transmitting nociceptive pain sensations Lawson, Voltage clamp experiments have shown that these TTX-sensitive channels are involved in amplifying subthreshold depolarizations, and are active during APs Vasylyev and Waxman, The slow-activating, slow-inactivating Nav1.
As a result, these TTX-resistant channels are of particular interest for treating neuropathic pain symptoms reviewed by Scholz and Woolf, Here, we investigate whether this mode of propagation is indeed possible, and its potential benefits in terms of basic constraints faced by neural fibers.
In stochastic simulations, the changes of conformations of ion channels were individually modeled Faisal, Simulations were based on biophysical data from Baker Computations were carried out using the Modigliani stochastic simulator Faisal et al. Membrane capacitance was set to 0. Our C-fiber model axon contains only two types of voltage gated ion channels. This transforms into a 5-state channel for stochastic simulation for details, see Faisal et al. We simulated both uniformly distributed channels and channels clustered on lipid rafts placed regularly along the 0.
Single channel conductance values are putative based on typical values for ion channels. We also simulate different cluster configurations length, distance based on previous work Zeng and Tang, although the results from those can not be directly compared to the uniform axon. For all lipid raft configurations i.
At each trial, we injected a small current step twice. The first evoked AP was only used to ensure the ion channels were properly initialized. We only used data from the second AP of each trial. Figure 1. Schematic view of axonal models. A The null-hypothesis axon. The width of each AP is measured between the half-width points. In deterministic simulations, the AP waveform is kept constant while propagating through the axon.
Figure 2. Action potential propagation in a 0. White areas signify no current flow. In addition, the stochastic opening of each discrete channel has a minimum current flow determined by the single channel conductance, that is larger than the minimum conductance allowed in the deterministic model.
Figure 3. Microsaltatory conduction in a 0. E Profile of the AP waveform propagating in a C-fiber axon. The bumps in the waveform correspond to the placement of lipid rafts. F Profile of the AP waveform in a model of mammalian myelinated axon using parameters from McIntyre et al. The height of the AP is only slightly lower outside of lipid rafts. Therefore, the membrane potential over the inter-raft region is roughly constant, and equal to that over lipid rafts.
Note that in myelinated axons, the amplitude of APs over the internodal regions is also not much lower than the amplitude in nodes of Ranvier Bakiri et al. This is also confirmed by our simulations of a mammalian myelinated axon model see Figure 3F , based on data from McIntyre et al. AP waveforms are slightly wider over lipid rafts in both deterministic Figure 3A and stochastic Figure 3B simulations.
We investigated the influence of the length l of rafts, and the distance between them L on the shape of action potential. The results are plotted in Figure 4. Both AP width and height seem affected by the size and placement of lipid rafts. Longer rafts increase the width of APs almost linearly Figure 4A. Increasing the distance between lipid rafts, on the other hand, shortens the width of APs. With 0. Figure 4. Action potential height and width as functions of channel distributions.
While varying the inter-raft distance, the lipid raft length was set to 0. We treat this question in Section 3. The change in the shape of APs directly results into changes in their metabolic cost Figure 5. Increasing the distance between rafts also reduces the metabolic cost.
The profile of the variation in metabolic cost closely follows that of change in AP width, suggesting that width, rather than height, determines the metabolic cost of firing APs Figures 4A,C , 5.
Figure 5. Metabolic cost of action potentials as functions of lipid raft configuration in a 0. Lipid raft length was set to 0.
In our simulation, this does not result in a significant change of metabolic cost. In stochastic simulations, the opening of a channel means that a conductance equal to that of the single channel is added to the membrane.
This minimum current due to the discrete nature of ion channel conductance has an impact on the metabolic cost of APs. Figure 6. Metabolic cost of action potentials for different channel distributions in a 0. Data was obtained using both deterministic blue lines and stochastic boxes simulations.
On each box, the central mark is the median, the edges of the box are the 25th and 75th percentiles, the whiskers extend to the most extreme data points not considered outliers, and outliers are plotted individually. Shortening the lipid rafts to 0. Due to their very small diameter, it is extremely difficult to obtain intracellular data from C-fibers, and therefore we can only estimate the propagation velocity in these fibers using extracellular recordings Tigerholm et al. These estimations can not be reliably linked to axonal diameter.
C-fiber axons are known for their very low conduction velocities. In stochastic simulations, we obtained a comparable median value. However, as was the case with the metabolic cost of APs, shortening lipid rafts or increasing the distance between them resulted in a reduction of the AP propagation velocity.
How does Saltatory conduction occur? Saltatory conduction describes the way an electrical impulse skips from node to node down the full length of an axon, speeding the arrival of the impulse at the nerve terminal in comparison with the slower continuous progression of depolarization spreading down an unmyelinated axon.
Why are there nodes of Ranvier? Nodes of Ranvier are gaps in the myelin sheath coating on the neural axon. The nodes of Ranvier allow for ions to diffuse in and out of the neuron, propagating the electrical signal down the axon. Since the nodes are spaced out, they allow for saltatory conduction, where the signal rapidly jumps from node to node. What is continuous and saltatory conduction? Continuous Conduction ion flow.
Through their VGchannels in each adjacent segment of the membrane. Saltatory conduction. A means by which action potentials jump from node to node along an axon. What is continuous propagation? When an action potential in an axon spreads to a neighboring region of its membrane by a series of small steps, the process is called continuous propagation.
When it propagates by jumping from one site to another along the axon, the process is called saltatory propagation. What are the advantages of Saltatory conduction quizlet?
Terms in this set 5 In the vertebrates. What is saltatory conduction? The jumping of action potentials from node to node, it has the benefit of conserving energy, instead of admitting Na ions at every point along the axon, and then having to pump them out via the Na,K pump, a myelinated axon admits only at its nodes.
Why are myelinated nerves faster? Neurons with myelin or myelinated neurons conduct impulses much faster than those without myelin. Because the impulse 'jumps' over areas of myelin, an impulse travels much faster along a myelinated neuron than along a non-myelinated neuron. Myelin is a fatty white substance, made mainly up of cholesterol, acts as an insulation around a wire.
The myelin sheath is wrapped around an axon in such a fashion, that there are a few gaps in between, these are called the Nodes of Ranvier. Simply put the impulse jumps from one node to the other node, hence called Saltatory Conduction. Unlike the wiring in outer world, which conducts electricity by the shifting of electrons, within these biological wires the impulses are conducted through hyperpolarizing or depolarizing the membrane.
It is slightly tricky, but I will try to explain it as easily I can. Now, there are alot of ion channels on the cell membrane neurilemma of the nerve cells. These ion channels selectively allow some ions to pass through them, and prevent some of the ions. Now, because of these ion channels, there will be a difference in the net charge either positive or negative on either side of this membrane.
0コメント